CN102746289B - The preparation method of a kind of lurasidone hydrochloride - Google Patents
The preparation method of a kind of lurasidone hydrochloride Download PDFInfo
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- CN102746289B CN102746289B CN201210131007.8A CN201210131007A CN102746289B CN 102746289 B CN102746289 B CN 102746289B CN 201210131007 A CN201210131007 A CN 201210131007A CN 102746289 B CN102746289 B CN 102746289B
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Abstract
The present invention discloses a kind of preparation method such as formula the lurasidone hydrochloride shown in (I), it comprises the following step: can the organic solvent miscible with water and hydrochloric acid composition mixture, process compound (II) is not containing more than the solution in the dialkyl ketone solvent of 6 carbon atoms, crystallization; Described can the mass ratio of the organic solvent miscible with water and hydrochloric acid be 0.5: 1 to 100: 1; The described hydrogenchloride in hydrochloric acid and the mol ratio of Compound I I are 10: 1 to 0.9: 1. The wearing quality of the preparation method of the present invention significantly improves, and preparation-obtained lurasidone hydrochloride (Compound I) purity height, acetone residue are low, and receipts rate height is more economical, is suitable for suitability for industrialized production.
Description
Technical field
The present invention is specifically related to the preparation method of a kind of lurasidone hydrochloride.
Background technology
Lurasidone hydrochloride (lurasidonehydrochloride), also known as Lurasidone HCl, can be used for the treatment of mental disorder (such as schizophrenia). Its chemical structure is as shown in structural formula I.
According to the report of patent documentation JP-A-5-17440 and patent families EP0464846 thereof, above-claimed cpd I can with the aqueous isopropanol of hydrogenchloride process its free alkali (Compound I I) acetone soln obtain, but aforesaid method is not suitable for large-scale industrial production.
Separately according to the report of Chinese patent 200480022168.7, it is necessary to the acetone soln of the HCl treatment Compound I I with 1.8% to 5.0% just can obtain the lurasidone hydrochloride (Compound I) of low acetone residue, receipts rate lower (85%). When being greater than the hydrochloric acid of 5.0% by concentration, when preparing Compound I by method described in this patent, the acetone residue of gained Compound I is greater than 0.5%. According to " chemicals residual solvent investigative technique governing principle " that State Food and Drug Administration's drug evaluation center is promulgated, in chemicals, the limit of acetone residue amount is 0.5%. When being the hydrochloric acid of 1.8% by concentration, when preparing Compound I by method described in this patent, the receipts rate of gained Compound I is only 65%. Therefore, when aforesaid method is applied to large-scale industrial production, there is limitation.
Summary of the invention
Technical problem to be solved by this invention is in the preparation method in order to overcome existing lurasidone hydrochloride, need relatively severe condition just can obtain the defect of lurasidone hydrochloride of low acetone residue, high purity, high receipts rate, and provide the preparation method of the high lurasidone hydrochloride of a kind of wearing quality. Lurasidone hydrochloride (Compound I) purity height, acetone residue that the preparation method of the present invention obtains are low, receipts rate height, more economical, are suitable for suitability for industrialized production.
Therefore, the present invention provides a kind of preparation method such as formula the lurasidone hydrochloride shown in (I), and it comprises the following step: can the organic solvent miscible with water and the mixture of hydrochloric acid composition, process the solution of compound (II) in hydrophilic solvent, crystallization; Described can the mass ratio of the organic solvent miscible with water and hydrochloric acid be 0.5: 1 to 100: 1; The described hydrogenchloride in hydrochloric acid and the mol ratio of Compound I I are 10: 1 to 0.9: 1;
Wherein, described can the organic solvent miscible with water be: methyl alcohol, ethanol, Virahol, n-propyl alcohol, propyl carbinol, sec-butyl alcohol, isopropylcarbinol, ethylene glycol, 1,2-propylene glycol, 1, ammediol, 1,4-butyleneglycol, 2, one or more in 3-butyleneglycol, 1,5-pentanediol, 1,6-HD, glycerine, acetone, butanone, acetonitrile, tetrahydrofuran (THF) and 2-methyltetrahydrofuran etc. Can the organic solvent miscible with water be preferably: one or more in acetone, butanone, ethanol, Virahol, n-propyl alcohol, sec-butyl alcohol, acetonitrile and tetrahydrofuran (THF). Preferred can the organic solvent miscible with water be: one or more in acetone, butanone and ethanol.
Wherein, described hydrophilic solvent comprises one or more in ketones solvent, alcoholic solvent, ether solvent and nitrile solvents, it is preferable that ketones solvent and/or alcoholic solvent, it is more preferable to be ketones solvent. Ketones solvent is preferably containing not more than the dialkyl ketone of 6 carbon atoms, such as one or more in acetone, butanone (being also called methyl ethyl ketone) and 4-methyl-2 pentanone etc. Preferred ketones solvent is acetone and/or butanone, it is most preferred that be acetone. Alcoholic solvent can be containing not more than the alcohol of 6 carbon atoms, such as one or more in Virahol, ethanol, methyl alcohol and ethylene glycol etc., it is preferable that Virahol and/or ethanol. Ether solvent can be containing not more than the ether of 6 carbon atoms, such as tetrahydrofuran (THF) and/or 2-methyltetrahydrofuran. Nitrile solvents can be containing not more than the nitrile of 6 carbon atoms, such as one or more in acetonitrile, butyronitrile and succinonitrile.
In the present invention, described hydrochloric acid is the aqueous solution of hydrogenchloride (HCl), its concentration all represents with massfraction (massfraction), refer to hydrogenchloride (solute) quality and hydrochloric acid (solution) mass ratio (w/w), it is expressed as a percentage. The concentration of described hydrochloric acid does not have particular requirement, it is possible to for lower concentration is to saturated solution, such as 0.3% to saturation concentration, it is preferable to 14% to 38%, it is more preferable to be 30% to 38%.
In the present invention, described can the mass ratio preferably 1: 1 to 60: 1 of the organic solvent miscible with water and hydrochloric acid, it is more preferable to 2: 1 to 30: 1.
In the present invention, the described hydrogenchloride in hydrochloric acid and the mol ratio of Compound I I are preferably 3: 1 to 1: 1, it is more preferable to be 1.3: 1 to 1: 1.
In the present invention; described Compound I I is not that Compound I I is dissolved in the solution containing in not more than the dialkyl ketone of 6 carbon atoms and being formed completely more than the solution in the dialkyl ketone of 6 carbon atoms containing; guarantee that Compound I I is dissolved in containing in not dialkyl ketone more than 6 carbon atoms by the method for this area routine, as dissolved by Compound I I by heating (being preferably heated to backflow). Described Compound I I and can be 1: 5 to 1: 60 containing not mass ratio more than the dialkyl ketone of 6 carbon atoms, it is preferable to 1: 6 to 1: 25. Described containing not more than the preferred acetone of dialkyl ketone and/or the butanone of 6 carbon atoms.
In the present invention, can the organic solvent miscible with water and hydrochloric acid composition mixture, the mode of the solution of process compound (II) in hydrophilic solvent, also be exactly can the mixture of the organic solvent miscible with water and hydrochloric acid composition, be not particularly limited with the hybrid mode of the solution of Compound I I in hydrophilic solvent. Such as, it is possible to can the organic solvent miscible with water and hydrochloric acid composition mixture be added in the solution of Compound I I in hydrophilic solvent; The solution of Compound I I in hydrophilic solvent can also be added to can the organic solvent miscible with water and hydrochloric acid composition mixture in.
The mixing mixture of the organic solvent miscible with water and hydrochloric acid composition " can " and the time needed for " solution of Compound I I in hydrophilic solvent " are not particularly limited. Such as, it is possible to by both disposable short mix, it is also possible to one material is slowly added in another kind of material. Preferably adopt the mode of slowly mixing, in this case, it is necessary to time be 1 minute to 6 hours, it is preferable that between 3 minutes to 3 hours, it is more preferable between 10 minutes to 1 hour.
In the present invention, the working method of described crystallization is not particularly limited, and the technique means usually taking this area conventional ensures that crystallization is abundant, as promoted that crystal precipitates out by operations such as cooling and stirrings. The speed of cooling of cooling crystallization is without the need to specifying, it is possible to cooling or programmed cooling fast, it is preferable that programmed cooling. Gained lurasidone hydrochloride (I) crystallization is separated by common means, as filtered. Before filtration, the temperature of crystallization reaction slurries remains on-20��65 DEG C usually, it is preferable that at-10��30 DEG C, it is more preferable at 10��25 DEG C.
It is separated the lurasidone hydrochloride obtained and can be removed solvent by drying. Drying mode also has no special requirements, such as, it is possible to drying under reduced pressure, constant pressure and dry, by circulation rare gas element or the dry air such as nitrogen. Drying temperature also has no special requirements, such as, it is possible at 0��100 DEG C, it is preferable that 40��70 DEG C.
Without prejudice to the field on the basis of common sense, above-mentioned each optimum condition, can arbitrary combination, obtain each better embodiment of the present invention.
Agents useful for same of the present invention and raw material are all commercially.
The positive progressive effect of the present invention is: adopts the method for the present invention to prepare lurasidone hydrochloride (I), achieves unexpected remarkable excellent results. The acetone residue of the lurasidone hydrochloride (I) of gained is less than 0.2%. High performance liquid chromatography (HPLC) purity of the lurasidone hydrochloride (I) of gained is greater than 99.85%, and maximum list is assorted is less than 0.1%; And the preparation method of the present invention can reach the high effect of receipts rate. Especially, the preparation method of the present invention compared to existing technology wearing quality significantly improve, it is not necessary to severe condition, it is to increase the stability of technique and reliability, be more suitable for suitability for industrialized production.
Embodiment
Below by the mode of embodiment, the present invention is described further, but does not therefore limit the present invention among described scope of embodiments. The experimental technique of unreceipted concrete condition in the following example, conventionally and condition, or selects according to catalogue.
Embodiment 1
By (3aR, 4S, 7R, 7aS)-2-[(1R, 2R)-2-[4-(1,2-benzisothiazole-3-base) piperazine-1-ylmethyl] cyclohexyl methyl] six hydrogen-1H-4,7-methyl isoindole 1,3-diketone (Compound I I) (5g) heating for dissolving are in acetone (53g). At reflux, drip acetone (12g) solution of the hydrochloric acid (1.13g) that adds 36%, dropwise rear return stirring 2h, after cool to room temperature, filter, namely obtain lurasidone hydrochloride (5.16g, receipts rate 96%) after 60 DEG C of vacuum-dryings: HPLC purity 99.86%, maximum list assorted 0.06%, acetone residue amount 0.13%.
Embodiment 2
By (3aR, 4S, 7R, 7aS)-2-[(1R, 2R)-2-[4-(1,2-benzisothiazole-3-base) piperazine-1-ylmethyl] cyclohexyl methyl] six hydrogen-1H-4,7-methyl isoindole 1,3-diketone (Compound I I) (2g) heating for dissolving are in acetone (21.2g). At reflux, drip acetone (6.5g) solution of the hydrochloric acid (0.91g) that adds 18%, dropwise rear return stirring 2h, after cool to room temperature, filter, namely obtain lurasidone hydrochloride (2.14g, receipts rate 99%) after 60 DEG C of vacuum-dryings: HPLC purity 99.83%, maximum list assorted 0.06%, acetone residue amount 0.21%.
Embodiment 3
By (3aR, 4S, 7R, 7aS)-2-[(1R, 2R)-2-[4-(1,2-benzisothiazole-3-base) piperazine-1-ylmethyl] cyclohexyl methyl] six hydrogen-1H-4,7-methyl isoindole 1,3-diketone (Compound I I) (2g) heating for dissolving are in acetone (21.2g). At reflux, drip acetone (6.5g) solution of the hydrochloric acid (1.13g) that adds 14.4%, add same temperature after dropwising and stir 2h, after cool to room temperature, filter, namely obtain lurasidone hydrochloride (1.95g, receipts rate 95%) after 60 DEG C of vacuum-dryings: HPLC purity 99.83%, maximum list assorted 0.07%, acetone residue amount 0.051%.
Embodiment 4
By (3aR, 4S, 7R, 7aS)-2-[(1R, 2R)-2-[4-(1,2-benzisothiazole-3-base) piperazine-1-ylmethyl] cyclohexyl methyl] six hydrogen-1H-4,7-methyl isoindole 1,3-diketone (Compound I I) (2g) heating for dissolving are in acetone (21.2g). At reflux, drip acetone (6.5g) solution of the hydrochloric acid (2.26g) that adds 7.2%, add same temperature after dropwising and stir 2h, after cool to room temperature, filter, namely obtain lurasidone hydrochloride (1.94g, receipts rate 90%) after 60 DEG C of vacuum-dryings: HPLC purity 99.81%, maximum list assorted 0.07%, acetone residue amount 0.097%.
Embodiment 5
By (3aR, 4S, 7R, 7aS)-2-[(1R, 2R)-2-[4-(1,2-benzisothiazole-3-base) piperazine-1-ylmethyl] cyclohexyl methyl] six hydrogen-1H-4,7-methyl isoindole 1,3-diketone (Compound I I) (2g) heating for dissolving are in acetone (21.2g). At reflux, drip acetone (6.5g) solution of the hydrochloric acid (0.65g) that adds 25%, add same temperature after dropwising and stir 2h, after cool to room temperature, filter, namely obtain lurasidone hydrochloride (2.04g, receipts rate 95%) after 60 DEG C of vacuum-dryings: HPLC purity 99.88%, maximum list assorted 0.04%, acetone residue amount 0.22%.
Embodiment 6
By (3aR, 4S, 7R, 7aS)-2-[(1R, 2R)-2-[4-(1,2-benzisothiazole-3-base) piperazine-1-ylmethyl] cyclohexyl methyl] six hydrogen-1H-4,7-methyl isoindole 1,3-diketone (Compound I I) (2g) heating for dissolving are in acetone (21.2g). At reflux, drip acetone (12g) solution of the hydrochloric acid (0.45g) that adds 36%, add same temperature after dropwising and stir 2h, after cool to room temperature, filter, namely obtain lurasidone hydrochloride (2.05g, receipts rate 95%) after 60 DEG C of vacuum-dryings: HPLC purity 99.87%, maximum list assorted 0.06%, acetone residue amount 0.24%.
Embodiment 7
By (3aR, 4S, 7R, 7aS)-2-[(1R, 2R)-2-[4-(1,2-benzisothiazole-3-base) piperazine-1-ylmethyl] cyclohexyl methyl] six hydrogen-1H-4,7-methyl isoindole 1,3-diketone (Compound I I) (2g) heating for dissolving are in acetone (21.2g). At reflux, drip ethanol (7g) solution of the hydrochloric acid (0.45g) that adds 36%, add same temperature after dropwising and stir 2h, after cool to room temperature, filter, namely obtain lurasidone hydrochloride (1.95g, receipts rate 91%) after 60 DEG C of vacuum-dryings: HPLC purity 99.76%, maximum list assorted 0.11%, acetone residue amount 0.10%.
Embodiment 8
By (3aR, 4S, 7R, 7aS)-2-[(1R, 2R)-2-[4-(1,2-benzisothiazole-3-base) piperazine-1-ylmethyl] cyclohexyl methyl] six hydrogen-1H-4,7-methyl isoindole 1,3-diketone (Compound I I) (2g) heating for dissolving are in acetone (21.2g). At reflux, drip butanone (6.5g) solution of the hydrochloric acid (0.45g) that adds 36%, add same temperature after dropwising and stir 2h, after cool to room temperature, filter, namely obtain lurasidone hydrochloride (2.07g, receipts rate 96%) after 60 DEG C of vacuum-dryings: HPLC purity 99.87%, maximum list assorted 0.07%, acetone residue amount 0.38%.
Embodiment 9
By (3aR, 4S, 7R, 7aS)-2-[(1R, 2R)-2-[4-(1,2-benzisothiazole-3-base) piperazine-1-ylmethyl] cyclohexyl methyl] six hydrogen-1H-4,7-methyl isoindole 1,3-diketone (Compound I I) (2g) heating for dissolving are in acetone (21.2g). At reflux, drip acetone (12g) solution of the hydrochloric acid (0.45g) that adds 36%, add same temperature after dropwising and stir 2h, after cool to room temperature, filter, namely obtain lurasidone hydrochloride (2.09g, receipts rate 97%) after 60 DEG C of vacuum-dryings: HPLC purity 99.90%, maximum list assorted 0.06%, acetone residue amount 0.067%.
Embodiment 10
By (3aR, 4S, 7R, 7aS)-2-[(1R, 2R)-2-[4-(1,2-benzisothiazole-3-base) piperazine-1-ylmethyl] cyclohexyl methyl] six hydrogen-1H-4,7-methyl isoindole 1,3-diketone (Compound I I) (2g) heating for dissolving are in acetone (21.2g). At reflux, drip acetone (12g) solution of the hydrochloric acid (0.45g) that adds 36%, add same temperature after dropwising and stir 2h, after cool to room temperature, filter, namely obtain lurasidone hydrochloride (2.06g, receipts rate 96%) after 60 DEG C of vacuum-dryings: HPLC purity 99.84%, maximum list assorted 0.05%, acetone residue amount 0.078%.
Embodiment 11
By (3aR, 4S, 7R, 7aS)-2-[(1R, 2R)-2-[4-(1,2-benzisothiazole-3-base) piperazine-1-ylmethyl] cyclohexyl methyl] six hydrogen-1H-4,7-methyl isoindole 1,3-diketone (Compound I I) (2g) heating for dissolving are in acetone (21.2g). At reflux, drip acetone (12g) solution of the hydrochloric acid (0.9g) (2.2 equivalent) that adds 36%, add same temperature after dropwising and stir 2h, after cool to room temperature, filter, namely obtain lurasidone hydrochloride (2.29g, receipts rate 100%) after 60 DEG C of vacuum-dryings: HPLC purity 99.71%, maximum list assorted 0.09%, acetone residue amount 0.21%.
Embodiment 12
By (3aR, 4S, 7R, 7aS)-2-[(1R, 2R)-2-[4-(1,2-benzisothiazole-3-base) piperazine-1-ylmethyl] cyclohexyl methyl] six hydrogen-1H-4,7-methyl isoindole 1,3-diketone (Compound I I) (2g) heating for dissolving are in acetone (21.2g). At reflux, drip acetone (12g) solution of the hydrochloric acid (3.6g) (8.8 equivalent) that adds 36%, add same temperature after dropwising and stir 2h, after cool to room temperature, filter, namely obtain lurasidone hydrochloride (2.14g, receipts rate 99%) after 60 DEG C of vacuum-dryings: HPLC purity 99.77%, maximum list assorted 0.11%, acetone residue amount 0.069%.
Embodiment 13
By (3aR, 4S, 7R, 7aS)-2-[(1R, 2R)-2-[4-(1,2-benzisothiazole-3-base) piperazine-1-ylmethyl] cyclohexyl methyl] six hydrogen-1H-4,7-methyl isoindole 1,3-diketone (Compound I I) (2kg) heating for dissolving are in acetone (21.2kg). At reflux, drip acetone (12kg) solution of the hydrochloric acid (450g) that adds 36%, add same temperature after dropwising and stir 2h, after cool to room temperature, filter, namely obtain lurasidone hydrochloride (2.1kg, receipts rate 97%) after 60 DEG C of vacuum-dryings: HPLC purity 99.89%, maximum list assorted 0.05%, acetone residue amount 0.047%.
Experimental data and the result of table 1 embodiment 1��13 gather
HPLC purity and maximum single impurity in table 1 adopt the high performance liquid chromatograph of the anti-phase ODS post of configuration and UV detector to measure. Acetone residue is then utilize the gas chromatograph for determination with capillary column and hydrogen ion flame detector.
Comparative example 1
By (3aR, 4S, 7R, 7aS)-2-[(1R, 2R)-2-[4-(1,2-benzisothiazole-3-base) piperazine-1-ylmethyl] cyclohexyl methyl] six hydrogen-1H-4,7-methyl isoindole 1,3-dione compounds II (30g), acetone (350g) reflux dissolve. 55 DEG C drip, in 15min, the hydrochloric acid (6.78g) that adds 36% in above-mentioned system, DEG C insulated and stirred 1h that adds 60 after dropwising. Cooling reaction, to 0 DEG C, stirs 1h with at temperature, filters, and 60 DEG C of vacuum-dryings, obtain lurasidone hydrochloride (31.5g, receipts rate 98%): HPLC purity 99.06%, and maximum list assorted 0.29%, acetone residue amount: 1.850%, product is defective.
Comparative example 2
By (3aR, 4S, 7R, 7aS)-2-[(1R, 2R)-2-[4-(1,2-benzisothiazole-3-base) piperazine-1-ylmethyl] cyclohexyl methyl] six hydrogen-1H-4,7-methyl isoindole 1,3-dione compounds II (30g), acetone (350g) reflux dissolve. 55 DEG C drip, in 15min, the hydrochloric acid (13.56g) that adds 18% in above-mentioned system, DEG C insulated and stirred 1h that adds 60 after dropwising. Cooling reaction, to 0 DEG C, stirs 1h with at temperature, filters, and 60 DEG C of vacuum-dryings, obtain lurasidone hydrochloride (31.5g, receipts rate 97.7%): HPLC purity 99.15%, and maximum list assorted 0.18%, acetone residue amount: 1.650%, product is defective.
Comparative example 3
By (3aR, 4S, 7R, 7aS)-2-[(1R, 2R)-2-[4-(1,2-benzisothiazole-3-base) piperazine-1-ylmethyl] cyclohexyl methyl] six hydrogen-1H-4,7-methyl isoindole 1,3-dione compounds II (30g), acetone (350g) reflux dissolve. 55 DEG C drip, in 15min, the hydrochloric acid (16.95g) that adds 14.4% in above-mentioned system, DEG C insulated and stirred 1h that adds 60 after dropwising. Cooling reaction, to 0 DEG C, stirs 1h with at temperature, filters, and 60 DEG C of vacuum-dryings, obtain lurasidone hydrochloride (31.0g, receipts rate 96.2%): HPLC purity 99.47%, single impurity is less than 0.16%, and acetone residue amount: 1.550%, product is defective.
Comparative example 4
By (3aR, 4S, 7R, 7aS)-2-[(1R, 2R)-2-[4-(1,2-benzisothiazole-3-base) piperazine-1-ylmethyl] cyclohexyl methyl] six hydrogen-1H-4,7-methyl isoindole 1,3-diketone (Compound I I) (2g) heating for dissolving are in acetone (21.2g). At reflux, the hydrochloric acid (4.52g) that adds 3.6% is dripped. DEG C insulated and stirred 1h that adds 60 after dropwising. Cooling reaction, to 0 DEG C, stirs 1h with at temperature, filters, and 60 DEG C of vacuum-dryings, obtain lurasidone hydrochloride (1.64g, receipts rate 76%): HPLC purity 99.85%, maximum list assorted 0.05%, acetone residue amount 0.050%. Receipts rate is low.
Claims (6)
1. the preparation method such as formula the lurasidone hydrochloride shown in (I), it is characterized in that comprising the following step: can the organic solvent miscible with water and hydrochloric acid composition mixture, process compound (II) is not containing more than the solution in the dialkyl ketone solvent of 6 carbon atoms, crystallization; Described can the mass ratio of the organic solvent miscible with water and hydrochloric acid be 2:1 to 30:1; Described can the organic solvent miscible with water be: one or more in acetone, butanone and ethanol; Described is acetone containing not dialkyl ketone more than 6 carbon atoms; The concentration of described hydrochloric acid is 14% to 38% (w/w); The described hydrogenchloride in hydrochloric acid and the mol ratio of compound ii are 3:1 to 1:1;
2. preparation method as claimed in claim 1, it is characterised in that: the concentration of described hydrochloric acid is 30% to 38% (w/w).
3. preparation method as claimed in claim 1, it is characterised in that: hydrogenchloride and the mol ratio of compound ii in described hydrochloric acid are 1.3:1 to 1:1.
4. preparation method as claimed in claim 1, it is characterised in that: described Compound I I is being obtained containing not being dissolved in by Compound I I by heating more than the solution in the dialkyl ketone of 6 carbon atoms in containing not dialkyl ketone more than 6 carbon atoms.
5. preparation method as claimed in claim 4, it is characterised in that: described compound ii and be 1:5 to 1:60 containing not mass ratio more than the dialkyl ketone of 6 carbon atoms.
6. preparation method as claimed in claim 5, it is characterised in that: described compound ii and be 1:6 to 1:25 containing not mass ratio more than the dialkyl ketone of 6 carbon atoms.
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| CN102911170A (en) * | 2012-11-15 | 2013-02-06 | 苏州第壹制药有限公司 | Method for preparing imide compound hydrochloride |
| CN105524057A (en) * | 2013-03-06 | 2016-04-27 | 江苏恩华药业股份有限公司 | Lurasidone hydrochloride new crystal form and preparation method thereof |
| CN103539794A (en) * | 2013-10-17 | 2014-01-29 | 常州大学 | Salifying method of lurasidone hydrochloride |
| US10426770B2 (en) * | 2014-10-14 | 2019-10-01 | Jubilant Generics Limited | Process for the preparation of Lurasidone hydrochloride |
| CN106146486A (en) * | 2015-04-21 | 2016-11-23 | 上海医药集团股份有限公司 | A kind of method preparing high-purity high-yield Lurasidone |
| CN106496218A (en) * | 2016-10-20 | 2017-03-15 | 中国药科大学 | Based on the Lurasidone HCl nanocrystal preparation method that solubility relies on pH properties |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0464846A1 (en) * | 1990-07-06 | 1992-01-08 | Sumitomo Pharmaceuticals Company, Limited | Imide derivatives, and their production and use |
| CN1832946A (en) * | 2003-07-29 | 2006-09-13 | 大日本住友制药株式会社 | Process for producing imide compound |
| WO2011136384A1 (en) * | 2010-04-26 | 2011-11-03 | Dainippon Sumitomo Pharma Co., Ltd. | A process of a quaternary ammonium salt using phosphate |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0464846A1 (en) * | 1990-07-06 | 1992-01-08 | Sumitomo Pharmaceuticals Company, Limited | Imide derivatives, and their production and use |
| CN1832946A (en) * | 2003-07-29 | 2006-09-13 | 大日本住友制药株式会社 | Process for producing imide compound |
| WO2011136384A1 (en) * | 2010-04-26 | 2011-11-03 | Dainippon Sumitomo Pharma Co., Ltd. | A process of a quaternary ammonium salt using phosphate |
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